A randomized, double-blind, crossover comparison of risperidone and haloperidol in Korean dementia patients with behavioral disturbances.

OBJECTIVE: Behavioral disturbances in dementia are extremely prominent and distressful, and often result in serious physical, social, and economic consequences. The authors compared the efficacy and tolerability of risperidone and haloperidol in the treatment of behavioral and psychological symptoms of dementia (BPSD) in institutionalized elderly Korean patients with Alzheimer disease, vascular dementia, or mixed dementia. METHODS: This was an 18-week double-blind, crossover study involving 120 patients who were randomly assigned to receive flexible doses (0.5-1.5 mg/day) of risperidone or haloperidol. BPSD were assessed using the Korean version of the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD-K), the Korean version of the Cohen-Mansfield Agitation Inventory (CMAI-K), and the Clinical Global Impression of Change scale (CGI-C). Safety and tolerability assessments included the Extrapyramidal Symptom Rating Scale and the incidence of adverse events. RESULTS: Both risperidone and haloperidol were efficacious in alleviating BPSD. However, when receiving risperidone, patients showed significantly greater improvement than when receiving haloperidol in the total and subscale scores of the BEHAVE-AD-K, the total and subscale scores of the CMAI-K, and the scores on the CGI-C scale. Also, risperidone had an additional benefit on aggressiveness and anxieties/phobias. The risk of antipsychotic-induced parkinsonism throughout this study was significantly lower with risperidone than with haloperidol. CONCLUSION: Risperidone had a favorable efficacy and tolerability profile compared with haloperidol in the treatment of BPSD in this patient population.     

Lack of modifying effects of atrazine and/or tamoxifen on thyroid carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine (DHPN)

The modifying effects of atrazine, and/or tamoxifen, on thyroid carcinogenesis were investigated in a rat two-stage carcinogenesis model following N-bis(2-hydroxypropyl)nitrosamine (DHPN) initiation. Five-week-old male F344 rats were given a single subcutaneous injection of DHPN (2800 mg/kg, body weight) or vehicle alone. Starting 1 week later, the animals were fed a diet supplemented with 0, 5, 50 or 500 ppm of atrazine, 500 ppm atrazine plus 5 ppm tamoxifen, or 5 ppm tamoxifen in the DHPN-treated groups, and 0 or 500 ppm of atrazine in the DHPN-untreated groups for 24 weeks. At autopsy major organs, including the thyroid, pituitary, liver, kidney, testis, epididymis, and brain, were collected and histopathologically examined. Body weights were significantly (P<0.05) decreased by the high doses of atrazine or tamoxifen, the effect being enhanced in combination. Relative thyroid weights were significantly increased (P<0.05) only in the tamoxifen-treated group and pituitary weights were elevated with 500 ppm atrazine plus tamoxifen (P<0.05). Relative liver weights were increased by the high dose of atrazine. However, the atrazine and/or tamoxifen treatments did not induce significant histopathological changes in the major organs, including the thyroid, nor cause significant changes in serum TSH levels. These results suggest that neither atrazine nor tamoxifen may promote thyroid carcinogenesis, alone as well as in combination.     

Heterogeneity of IgE response to TDI-HSA conjugates by ELISA in toluene diisocyanate (TDI) -induced occupational asthma (OA) patients.

Toluene diisocyanate (TDI), a low molecular weight reactive chemical, is known to be a main cause of occupational asthma (OA) in Korea. Although it is thought that inhaled TDI may act as a hapten, the precise mechanisms of TDI-induced OA are unknown. In this study, TDI-human serum albumin (HSA) conjugates (5, 10, 20 and 30 min) were prepared in the range of 1.5 to 5.0 TDI mole/HSA mole. Specific binding of serum IgE to TDI-HSA (30 min) was observed using IgE ELISA as well as ELISA inhibition assay. Around 40% of TDI-induced OA patients were positive for serum specific IgE by ELISA. Degrees of serum IgE binding were different depending on which TDI-HSA conjugate was used as an antigen. Moreover, binding patterns were different depending on the individuals. Interestingly, higher binding of IgE to TDI-HSA (5 min) than to TDI-HSA (30 min) which was more highly substituted was observed in some patients. Probably new antigenic epitopes on carrier proteins were targets of the specific IgE. The results of this study indicated that IgE responses to TDI-HSA conjugates were heterogeneous in TDI-induced OA patients and self-proteins modified by reactive chemicals can become a major target antigen of IgE in certain cases.     

A comparison of coarctation resection and subclavian flap angioplasty using ultrasonographically monitored postocclusive reactive hyperemia

The reported relatively high incidence of early restenosis at the coarctation repair site with subclavian flap angioplasty, especially in infants less than 3 months of age, prompted a physiologically oriented analysis of relief of obstruction from coarctation after subclavian flap angioplasty versus resection and end-to-end anastomosis in infancy. Twenty-one patients who had undergone repair of coarctation in infancy by either subclavian flap angioplasty (nine patients) (median age 8 years) or resection and end-to-end anastomosis (12 patients) (median age 8 years) were evaluated by Doppler spectrum analysis of the blood flow velocities in the femoral artery at rest and during reactive hyperemia. The median resting right upper to lower limb systolic pressure difference (with interquartile range) was similar in the angioplasty, resection and anastomosis, and control groups: -5 mm Hg (18 mm Hg), 0 mm Hg (12 mm Hg), and -2.5 mm Hg (10 mm Hg), respectively. Also, similar resting values for the maximum frequency of the advancing curve and the pulsatility and resistance indices were measured in the three groups. During reactive hyperemia of the leg, however, a significant hemodynamic obstruction across the repair site became clinically manifest in the angioplasty group only, as documented by a lower pulsatility index in comparison with the control group (p = 0.01, Mann-Whitney U test). Comparison of the hemodynamic results between the angioplasty and resection and anastomosis groups in subdivisions of infants operated on at an age of less or greater than 3 months, both at rest and during reactive hyperemia, showed, already at rest, a significantly lower value for the pulsatility index in the former angioplasty subdivision (p = 0.05, Student's t test), indicating a significant resistance at the coarctation repair site in the angioplasty patients operated on before the third month of life. A disadvantage of angioplasty (compared with resection and anastomosis) was noted when angioplasty was performed before the third month of life, and an unequivocal lack of advantage was noted when performed beyond that period regarding relief of obstruction from coarctation. In addition, a definite potential for adverse long-term effects on the hemodynamics of the left upper limb after subclavian flap angioplasty in infancy has been documented. For these reasons we prefer to perform resection and end-to-end anastomosis for repair of coarctation in infancy.     

Herpetic croup: two case reports and a review of the literature

Croup is an acute infectious illness usually occurring in children; it is characterized by brassy cough and stridor. The main pathogens include mainly parainfluenza and influenza viruses. Recently there have been reports of prolonged croup caused by the herpes simplex viruses. We report two cases of prolonged croup due to herpes simplex types 1 and 2. We also review and summarize the reported pediatric cases of herpetic croup.     

Specificity of co-promoting effects of caffeine on thyroid carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine

The specificity of copromotion effects of caffeine with known goitrogenic factors on thyroid carcinogenesis was examined in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Male F344 rats were divided into 8 groups, each consisting of 10 animals, and received a single sc injection of 2,800 mg/kg DHPN. From one week after the DHPN initiation, they were given basal diet, iodine deficiency (ID) diet, 500 ppm phenobarbital (PB) solution or 1,000 ppm sulfadimethoxine (SDM) solution with or without 1,500 ppm caffeine feeding for 12 weeks. The caffeine, PB, SDM, and ID treatments significantly (p < 0.05 or 0.01) increased the relative thyroid weights, and the increases with PB or ID were further (p < 0.05 or 0.01) enhanced in combination with caffeine. SDM drastically promoted thyroid carcinogenesis in association with increased serum TSH levels regardless of the caffeine treatment. Thyroid follicular carcinomas and adenomas were more frequently observed in the additional caffeine groups than in the ID alone groups. The incidence and multiplicity of focal thyroid follicular hyperplasias in the ID-treated groups were significantly (p < 0.05 and 0.01) elevated in the case of combination with caffeine. Increases in serum TSH levels with PB or ID were also further enhanced in combination with caffeine. Serum thyroid hormone levels were significantly (p < 0.01) decreased by SDM but significantly (p < 0.05 or 0.01) increased by caffeine, PB or ID. Our results clearly indicate that dietary caffeine at a high dose of 1,500 ppm interacts with ID, but neither SDM nor PB, to promote rat thyroid carcinogenesis although the combined caffeine + PB treatment somewhat affected thyroid weights as well as thyroid hormone levels.     

Reticuloendothelial Fc receptor function in SLE patients. I. Primary HLA linked defect or acquired dysfunction secondary to disease activity?

Reticuloendothelial system (RES) Fc receptor-mediated immune clearance was measured in 18 patients with systemic lupus erythematosus (SLE). Only two patients, with major disease activity, had a prolonged T 1/2 of the blood disappearance curve of injected IgG coated red cells in comparison to 22 healthy controls. Circulating immune complexes (CIC) were studied with three methods: PEG precipitation, C1q-ELISA and the indirect granulocyte phagocytosis test (IGFT). The T 1/2 of the blood disappearance curve related significantly to the IGFT (r = 0.55, P less than 0.05) and not to the PEG and C1q-ELISA test. Although HLA-DR3 phenotype frequency was significantly increased in our SLE population (P less than 0.05), it was not related to Fc receptor function. Similarly, HLA-DR2 phenotype was not related to RES Fc receptor function. These data do not support the concept that a genetic HLA linked defect in reticuloendothelial Fc receptor function is a primary cause of SLE, predisposing the inflicted individual to immune complex deposition. However, Fc receptor-mediated immune clearance seems to be related to disease activity itself and to levels of CIC.     

Primitive Neuroectodermal Tumors of the Central Nervous System

Controversial issues relating to the pathobiology and classification of central nervous system primitive neuroectodermal tumors (PNETs) have plagued neuropathologists for more than 70 years. Hypotheses advanced in the mid-1920's have remained as fixed concepts in contemporary literature, largely consequent to repetitious support by a small number of neuropathologists despite a growing body of information discrediting these ideas from neuroembryologists, oncologists, neuroscien-tists and pathologists.
Attention has largely focused upon PNETs arising in the cerebellum (commonly known as medul-loblastomas [MBs]), because about 80% of central nervous system (CNS) PNETs originate in this site. It has been asserted that the 20% which do not are biologically different, although most individuals agree that the histological features of PNETs that occur in different sites throughout the CNS are indistinguishable from those growing in the cerebellum.
The historical aspects of this controversy are examined in the face of evidence that there is, in fact, a unique class of CNS tumors which should appropriately be regarded as primitive neuroectodermal in nature. Specifically, a number of different approaches to the problem have yielded data supporting this hypothesis. These approaches include the identification of patterns of expression among a variety of cellular antigens (demonstrated by the use of immunopathological techniques), molecular analyses of cell lines derived from these tumors, experimental production of PNETs and molecular genetic analyses.
Differences of opinion among surgeons, oncologists and radiotherapists are typically resolved by conducting cooperative studies of patients with these tumors who are diagnosed and treated at multiple centers.